A Genome-wide Scan for Primary Open-angle Glaucoma in a Black Population

Abstract

Abstract: : Purpose: To present the results of a genome-wide scan for primary open-angle glaucoma (POAG) in a population of African descent from the Barbados Family Study of Open-angle Glaucoma (BFSG). Methods: The study examination included a complete ophthalmologic evaluation, best corrected visual acuity, perimetry, tonometry, anthropometric and other measurements, fundus photography, a detailed interview and venipuncture for glycosylated hemoglobin and genotyping. POAG was defined as the presence of visual field and optic disc abnormalities in at least one eye, after the exclusion of other possible causes by the ophthalmologist. Linkage calculations were done with FASTLINK and SimIBD and were based on models and parameter estimates derived from a segregation analysis of these families, as well as model-free analyses. Locus-heterogeneity tests were done with the HOMOG program. Results. The linkage findings are based on 1327 individuals from 146 families. Two-point LOD scores >1.0 were identified on chromosomes 1, 2, 9, 10, 11 and 14, with increased multipoint LOD scores found on chromosomes 2, 10 and 14. Fine mapping indicated that POAG may be linked to intervals on chromosome 2q between D2S2188 and D2S2178 and chromosome 10p between D10S1477 and D10S601. Heterogeneity testing strongly supports linkage for POAG to at least one of these regions and suggests possible linkages to both. Conclusions. Findings from the BFSG indicate that POAG may be linked to regions on chromosome arms 2q and 10p. Although TIGR/Myocilin and Optineurin mutations have been causally linked to POAG in other populations, findings from this study do not support either of these as causative genes in an Afro-Caribbean population known to have relatively high rates of POAG. The findings presented require further replication or substantiation by the identification of causative genes.

Keywords: gene mapping